A Phase 1 interventional study of Intratumoral (IT) Poly ICLC 0.5 mg and Intratumoral (IT) Poly ICLC 1.0 mg in Prostate Cancer, sponsored by Ashutosh Kumar Tewari. Completed at 1 site in United States. Open to male participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2022-09-10.
Sponsored by Ashutosh Kumar Tewari · Phase 1, Interventional, and Treatment
The purpose of this study is to test an approach of stimulating the body's immune system to attack prostate cancer. This study will test injection of a substance polylysine and carboxymethylcellulose (Poly-ICLC, Hiltonol®)through a needle guided by MRI (magnetic resonance imaging) ultrasound fusion technology into the prostate gland. Poly ICLC has been used to help the body in its fight against cancer. The first aim of the study is to determine the highest dose of a substance Poly-ICLC (Hiltonol®) that can be safely tolerated by the study participants. The second aim of the study is to find out the toxicity or side effects of poly-ICLC.
This is a pilot dose escalation study of IT/IM Poly-ICLC in patients with high risk clinically localized prostate cancer. The dose and frequency of IT injections will be increased in successive cohorts to define a safe dose and schedule for further testing.
Intratumoral + intramuscular poly-ICLC in patients with clinical localized prostate cancer. In the current pilot clinical trial, poly-ICLC will be administered intratumorally (Artemis guided) and intramuscularly (e.g., deltoid muscle) prior to prostatectomy in patients with clinically localized prostate cancer. Based on the available preclinical data exploring intratumoral administration of PAMPs described above, we expect this approach will result in three immunomodulatory steps26:
Immunomodulatory Step 1: Innate immune local tumor killing induced by intratumoral poly-ICLC - the initial intratumoral injections are expected to induce activation/recruitment of IL-12, TNF-α, and other cytokines and NK cells, resulting in early tumor killing and antigen release.9-11 Poly-ICLC may also have a direct antiproliferative effect on tumor cells mediated by interferon-inducible nuclear enzyme systems.
Immunomodulatory Step 2: Th1 and cytotoxic T lymphocyte priming as a result of the repeated in-situ poly-ICLC 'danger signal' combined with the tumor antigens released in step 1 and further processed and cross-presented by poly-ICLC-activated myeloid dendritic cells.7,8 Poly-ICLC is expected to recruit myeloid dendritic cells and macrophages to the tumor site where they can load with antigens being released through the innate mechanisms, present them Th1 cells, and cross-present them to CD8 T cells in the tumor or in the regional lymph nodes, thus generating antigen specific cytotoxic T lymphocytes.
Immunomodulatory Step 3 (or "Boost" phase): Maintenance of the systemic anti-tumor immune response and migration of cytotoxic T lymphocytes to remote metastases, through repeated intramuscular poly-ICLC induction of chemokines, other costimulatory factors, and inflammasome activation.23-25 The rationale for followup with intramuscular maintenance is that as part of the comprehensive response, dsRNAs such as poly-ICLC induce various chemokines and costimulatory factors that help target the response to tumor. For example, one of these costimulatory factors is OX40, which belongs to the tumor necrosis factor family of cytokines, and helps maintain cytotoxic lymphocyte longevity and action at the tumor and metastatic sites.
6,484 studies on the registry are indexed under Prostatic Neoplasms; 1,415 are open to participants now.
This study's enrollment of 13 is below the median of 58 across 4,908 interventional studies indexed under Prostatic Neoplasms.
Browse Prostatic Neoplasms studies →Ashutosh Kumar Tewari is the lead sponsor of 3 studies on the registry; 1 is open to participants now.
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Inclusion Criteria:
No characteristics suggesting a potential higher risk of infection with intraprostatic injections:
No treatment with any investigational agent for any medical condition within 28 days prior to being registered for protocol therapy.
Adequate end organ function as determined by the following laboratory values:
Males: (140 - Age in years) × Actual Body Weight in kg 72 × Serum Creatinine (mg/dL)
Intratumoral (IT) Poly ICLC 0.5 mg IT once/week (week 1) Intramuscular (IM) Poly ICLC 1 mg IM twice weekly (weeks 3-6) Followed by Radical Prostatectomy at Week 10
Biological: Intratumoral (IT) Poly ICLC 0.5 mg · Biological: Intramuscular (IM) Poly ICLC · Procedure: Radical Prostatectomy
Intratumoral (IT) Poly ICLC 0.5 mg IT once/week (week 1+2) Intramuscular (IM) Poly ICLC 1 mg IM twice weekly (weeks 3-6) Followed by Radical Prostatectomy at Week 10
Biological: Intratumoral (IT) Poly ICLC 0.5 mg · Biological: Intramuscular (IM) Poly ICLC · Procedure: Radical Prostatectomy
Intratumoral (IT) Poly ICLC 1.0 mg IT once/week (week 1) Intramuscular (IM) Poly ICLC 1 mg IM twice weekly (weeks 3-6) Followed by Radical Prostatectomy at Week 10
Biological: Intratumoral (IT) Poly ICLC 1.0 mg · Biological: Intramuscular (IM) Poly ICLC · Procedure: Radical Prostatectomy
Intratumoral (IT) Poly ICLC 1.0 mg IT once/week (week 1+2) Intramuscular (IM) Poly ICLC 1 mg IM twice weekly (weeks 3-6) Followed by Radical Prostatectomy at Week 10
Biological: Intratumoral (IT) Poly ICLC 1.0 mg · Biological: Intramuscular (IM) Poly ICLC · Procedure: Radical Prostatectomy
0.5 mg IT once/week (week 1)
1.0 mg IT once/week (week 1)
Also known as: Polyinosinic-polycytidylic acid stabilized with polylysine and carboxymethylcellulose
1 mg IM twice weekly (weeks 3-6)
Also known as: Polyinosinic-polycytidylic acid stabilized with polylysine and carboxymethylcellulose
as per standard care
Dose-Limiting Toxicity level
3+3 dose escalation rules to define a safe dose of preoperative intratumoral (IT) plus intramuscular (IM) Polyinosinic-polycytidylic acid stabilized with polylysine and carboxymethylcellulose (poly-ICLC, Hiltonol®) prior to radical prostatectomy
Time frame: Week 6
Number of adverse events
Safety as determined by the frequency of adverse events as per the Common Terminology for Adverse Events (CTCAE) version 4.0.
Time frame: Week 6
Time to PSA progression
The time to prostate-specific antigen (PSA) progression will be defined as the time to PSA \> 0.2 ng/mL
Time frame: up to Week 12
This study is completed, as verified in Sep 2022. You cannot join it, but the record below documents what was studied.
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Ashutosh Kumar Tewari